Abstract
BACKGROUND: Although previous studies have suggested that genetic risk factors can contribute to the development of prurigo nodularis (PN), little is known about the specific variants involved. OBJECTIVE: We aimed to test which genetic variants increase predisposition to PN by conducting a large genome-wide association study. METHODS: Five separate cohorts (4239 case patients with PN and 583,544 controls) were combined through genome-wide association study meta-analysis, and the results were validated by using the Michigan Genomics Initiative. Data from regulatory regions and expression quantitative trait loci were applied to investigate genetic mechanisms. RESULTS: We identified a genome-wide significant genetic signal for PN (P = 7.5 × 10(-13); odds ratio = 1.17) at the IL31 locus, which has also been associated with psoriasis, atopic dermatitis, and 2 suggestive significant signals (P ≤ 1 × 10(-6)) in chromosomes 2 and 6. The IL31 signal is located in a regulatory region for T cells and keratinocytes; interestingly, it occurs substantially more frequently in European individuals than in African individuals. CONCLUSION: Our results reinforce the role of genetics in PN and advance understanding of the mechanisms and their relationship with other pruritic inflammatory skin diseases.